How much oxygen in adult cardiac arrest?

Dell’Anna et al. Critical Care 2014, 18:555 http://ccforum.com/content/18/5/555 VIEWPOINT How much oxygen in adult cardiac arrest? Antonio Maria Dell’Anna, Irene Lamanna, Jean-Louis Vincent and Fabio Silvio Taccone* See related commentary by Gershengorn, http://ccforum.com/content/18/5/556 Abstract Although experimental studies have suggested that a high arterial oxygen pressure (PaO2) might aggravate post-anoxic brain injury, clinical studies in patients resuscitated from cardiac arrest (CA) have given conflicting results. Some studies found that a PaO2 of more than 300 mm Hg (hyperoxemia) was an independent predictor of poor outcome, but others reported no association between blood oxygenation and neurological recovery in this setting. In this article, we review the potential mechanisms of oxygen toxicity after CA, animal data available in this field, and key human studies dealing with the impact of oxygen management in CA patients, highlighting some potential confounders and limitations and indicating future areas of research in this field. From the currently available literature, high oxygen concentrations during cardiopulmonary resuscitation seem preferable, whereas hyperoxemia should be avoided in the post-CA care. A specific threshold for oxygen toxicity has not yet been identified. The mechanisms of oxygen toxicity after CA, such as seizure development, reactive oxygen species production, and the development of organ dysfunction, need to be further evaluated in prospective studies. Introduction Sudden cardiac arrest (CA) is the leading cause of death among adults worldwide [1,2]. In most patients, attempts at cardiopulmonary resuscitation (CPR) remain ineffective and spontaneous cardiac activity cannot be restored [3]. Among those patients who do achieve return of spontaneous circulation (ROSC), there are two key periods when death may occur: early (during the first three days), usually because of recurrent CA or severe cardiovascular failure resulting in multiple organ failure (MOF), and late (beyond day 3), usually secondary to withdrawal of life-sustaining therapies in the absence of neurological recovery [4]. Although several interventions, including target temperature management (TTM), have been introduced into the postCA care of these patients [5,6], conflicting results have been obtained [7], and these approaches are not sufficient to prevent the deleterious consequences of brain ischemia in all patients. During the post-CA care, secondary brain insult must be avoided [8] and optimization of brain oxygenation is likely to be an important component of brain recovery. The restoration of adequate systemic hemodynamics is a prerequisite to provide adequate cerebral blood flow in CA patients [9,10], but brain oxygenation is also determined by * Correspondence: Department of Intensive Care, Erasme Hospital, Université Libre de Bruxelles, Belgium, Route de Lennik 808, 1070 Brussels, Belgium the arterial oxygen content. Arterial oxygen pressure (PaO2) itself may influence brain cellular oxygen supply; if hypoxemia (that is, PaO2 of less than 60 mm Hg) is associated with poor outcomes after CA [11], a high PaO2 may also be detrimental in a vulnerable brain, as suggested in patients with traumatic brain injury or stroke [12,13]. The aims of this article are to review the potential mechanisms of oxygen toxicity after CA and to discuss the clinical impact of oxygen management on post-CA care. Post-cardiac arrest syndrome: the role of oxygen Post-cardiac arrest syndrome (PCAS) is a complex phenomenon, which shares several features with septic shock [7,14]. In particular, PCAS includes a systemic inflammatory response that can be triggered by the ischemia-reperfusion injury and also specific precipitating events, such as concomitant infections or heart disease. Moreover, PCAS can contribute to brain injury and myocardial dysfunction and can rapidly lead to MOF. The primary ischemia-reperfusion injury [15] activates various intracellular pathways, promoting ion concentration disequilibrium with increased intracellular levels of inorganic phosphate, lactate, and H+, and resulting in an influx of calcium into the cell [16], which aggravates mitochondrial dysfunction and eventually leads to programmed cellular death (apoptosis). After reperfusion has © 2014 Dell'Anna et al.; licensee BioMed Central Ltd. The licensee has exclusive rights to distribute this article, in any medium, for 12 months following its publication. After this time, the article is available under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Dell’Anna et al. Critical Care 2014, 18:555 http://ccforum.com/content/18/5/555 occurred, other mediators, including superoxide (O2−), peroxynitrite (NO2−), hydrogen peroxide (H2O2), and hydroxyl radicals (OH−), contribute to worsen cellular function by oxidizing and damaging numerous cellular components [17] (Figure 1). These reactive oxygen species (ROS) then have a central role in initiating and enhancing the post-ischemic damage [15]. Indeed, supra-normal oxygen concentrations in this context may further stimulate ROS production and contribute to worsen cellular function in a setting of impaired mitochondrial function and impaired oxygen utilization. Moreover, some other systemic detrimental effects of hyperoxemia have been known for many years [18-20]. Hyperoxemia causes systemic and coronary vasoconstriction, which can decrease cardiac output and induce myocardial ischemia. In some experimental models of global cerebral ischemia, hyperoxemia has been shown to be detrimental to the brain, probably also because of its vasoconstrictor effects [21,22]. Hyperoxemia may also provoke or exacerbate seizures, which could aggravate brain injury [23,24]. Oxygen therapy after cardiac arrest: animal studies Several studies have assessed the effects of administering high oxygen concentrations in experimental models of CA. Pilcher and colleagues [25] recently reviewed studies that evaluated the role of different oxygenation strategies that is, one with 100% inspired oxygen fraction (FiO2) and the other with lower FiO2 as a control - after ROSC. Six studies including 95 animals of different species were included in their final meta-analysis; in general, administration Page 2 of 7 of high FiO2 (100%) for 1 hour after ROSC resulted in a worse neurological outcome, as assessed by a neurological deficit score, than other FiO2 values. Four of the five studies that assessed histological damage reported a significantly higher neuronal injury with high FiO2; cerebral metabolic function was also more altered in t (...truncated)